The proposed research seeks to advance our understanding of the neural mechanisms underlying human spatial cognition. To accomplish this, I will study recordings from patients undergoing long-term intracranial epilepsy monitoring while they perform a virtual-navigation task. These intracranial recordings provide a unique opportunity to study human cognitive processes with a higher temporal resolution than can be obtained with conventional, noninvasive brain-imaging techniques. My proposed experiments examine the relation between neuronal spiking activity, brain waves (oscillations), and subjects' behavior during several variants of Yellow Cab, a virtual taxi-driver video game. My experiments are performed with the highest standard of care and pose only minimal risks for the patients beyond those already present to treat refractory epilepsy. This research will allow me to link the extensive literature on the electrophysiology of the rodent hippocampal formation during navigation with psychological research on human behavior in spatial tasks. The focus of Aim 1 is to build a functional map of the human brain based on how neurons across different brain regions respond to various aspects of navigational behavior. In particular, in widespread brain regions, I will characterize the prevalence of neurons with sensitivities for place, view, goal, and heading, as well as neurons responding to more complex variables such as "place-by-direction" cells and "grid" cells. Aim 2 probes the temporal relation between these navigation-related neuronal responses and the brain's ongoing theta (4-8 Hz) oscillations. Here, I will test the hypothesis that neurons represent distinct information by the timing of their spiking in relation to ongoing brain oscillations (phase coding), as suggested in recent studies of rodent electrophysiology. Aim 3 examines the neural basis of the observer-centered representations observed when people answer questions about an environment's layout. This will allow me to examine whether the same neural patterns used during navigation are also in use when people are not actively moving. Relevance of this research to public health: One goal of the proposed research is to create a functional map of the human brain during spatial navigation. This has direct relevance to the clinical treatment of epilepsy, in which cognitive mapping during surgical procedures is crucial for ensuring successful post surgical outcome. Furthermore, the proposed research may pave the way for more effective treatment of Alzheimer's disease in which spatial memory is impaired. [unreadable] [unreadable] [unreadable]